Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic membrane. EMBO J 2006 Apr 19;25(8):1623-34
Date
04/08/2006Pubmed ID
16601687Pubmed Central ID
PMC1440842DOI
10.1038/sj.emboj.7601065Scopus ID
2-s2.0-33646123087 (requires institutional sign-in at Scopus site) 115 CitationsAbstract
Intracellular membrane trafficking of glutamate receptors at excitatory synapses is critical for synaptic function. However, little is known about the specialized trafficking events occurring at the postsynaptic membrane. We have found that two components of the exocyst complex, Sec8 and Exo70, separately control synaptic targeting and insertion of AMPA-type glutamate receptors. Sec8 controls the directional movement of receptors towards synapses through PDZ-dependent interactions. In contrast, Exo70 mediates receptor insertion at the postsynaptic membrane, but it does not participate in receptor targeting. Thus, interference with Exo70 function accumulates AMPA receptors inside the spine, forming a complex physically associated, but not yet fused with the postsynaptic membrane. Electron microscopic analysis of these complexes indicates that Exo70 mediates AMPA receptor insertion directly within the postsynaptic density, rather than at extrasynaptic membranes. Therefore, we propose a molecular and anatomical model that dissects AMPA receptor sorting and synaptic delivery within the spine, and uncovers new functions of the exocyst at the postsynaptic membrane.
Author List
Gerges NZ, Backos DS, Rupasinghe CN, Spaller MR, Esteban JAAuthor
Nashaat Gerges PhD Chair, Professor in the School of Pharmacy Administration department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCarrier Proteins
Cells, Cultured
Dendritic Spines
Hippocampus
Membrane Fusion
Membrane Proteins
Mice
Mutation
Neurons
Organ Culture Techniques
Patch-Clamp Techniques
Protein Transport
Rats
Receptors, AMPA
Synapses
Synaptic Membranes
Synaptic Transmission
Synaptosomes
Vesicular Transport Proteins